The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

Autores
Vetter, Douglas E.; Katz, Eleonora; Maison, Stéphane F.; Taranda, Julian; Turcan, Sevin; Ballestero, Jimena Andrea; Liberman, M. Charles; Elgoyhen, Ana Belen; Boulter, Jim
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.
Fil: Vetter, Douglas E.. Tufts University School Of Medicine; Estados Unidos
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; Argentina
Fil: Maison, Stéphane F.. Harvard Medical School; Estados Unidos. Tufts University School Of Medicine; Estados Unidos. Massachusetts Eye And Ear Infirmary; Estados Unidos
Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School Of Medicine; Estados Unidos
Fil: Turcan, Sevin. Tufts University School Of Medicine; Estados Unidos
Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Liberman, M. Charles. Universidad de Buenos Aires; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; Argentina
Fil: Boulter, Jim. University of California at Los Angeles. School of Medicine; Estados Unidos
Materia
Cochlea
Electrophysiology
Inner Hair Cells
Outer Hair Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/80009
Acceder
id CONICETDig_2585a4007bad20e25e12da97340385a4
oai_identifier_str oai:ri.conicet.gov.ar:11336/80009
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear systemVetter, Douglas E.Katz, EleonoraMaison, Stéphane F.Taranda, JulianTurcan, SevinBallestero, Jimena AndreaLiberman, M. CharlesElgoyhen, Ana BelenBoulter, JimCochleaElectrophysiologyInner Hair CellsOuter Hair Cellshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.Fil: Vetter, Douglas E.. Tufts University School Of Medicine; Estados UnidosFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; ArgentinaFil: Maison, Stéphane F.. Harvard Medical School; Estados Unidos. Tufts University School Of Medicine; Estados Unidos. Massachusetts Eye And Ear Infirmary; Estados UnidosFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School Of Medicine; Estados UnidosFil: Turcan, Sevin. Tufts University School Of Medicine; Estados UnidosFil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Liberman, M. Charles. Universidad de Buenos Aires; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; ArgentinaFil: Boulter, Jim. University of California at Los Angeles. School of Medicine; Estados UnidosNational Academy of Sciences2007-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/80009Vetter, Douglas E.; Katz, Eleonora; Maison, Stéphane F.; Taranda, Julian; Turcan, Sevin; et al.; The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 51; 12-2007; 20594-205990027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0708545105info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2154476/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:01:10Zoai:ri.conicet.gov.ar:11336/80009instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:01:10.298CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
title The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
spellingShingle The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
Vetter, Douglas E.
Cochlea
Electrophysiology
Inner Hair Cells
Outer Hair Cells
title_short The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
title_full The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
title_fullStr The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
title_full_unstemmed The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
title_sort The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
dc.creator.none.fl_str_mv Vetter, Douglas E.
Katz, Eleonora
Maison, Stéphane F.
Taranda, Julian
Turcan, Sevin
Ballestero, Jimena Andrea
Liberman, M. Charles
Elgoyhen, Ana Belen
Boulter, Jim
author Vetter, Douglas E.
author_facet Vetter, Douglas E.
Katz, Eleonora
Maison, Stéphane F.
Taranda, Julian
Turcan, Sevin
Ballestero, Jimena Andrea
Liberman, M. Charles
Elgoyhen, Ana Belen
Boulter, Jim
author_role author
author2 Katz, Eleonora
Maison, Stéphane F.
Taranda, Julian
Turcan, Sevin
Ballestero, Jimena Andrea
Liberman, M. Charles
Elgoyhen, Ana Belen
Boulter, Jim
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cochlea
Electrophysiology
Inner Hair Cells
Outer Hair Cells
topic Cochlea
Electrophysiology
Inner Hair Cells
Outer Hair Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.
Fil: Vetter, Douglas E.. Tufts University School Of Medicine; Estados Unidos
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; Argentina
Fil: Maison, Stéphane F.. Harvard Medical School; Estados Unidos. Tufts University School Of Medicine; Estados Unidos. Massachusetts Eye And Ear Infirmary; Estados Unidos
Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School Of Medicine; Estados Unidos
Fil: Turcan, Sevin. Tufts University School Of Medicine; Estados Unidos
Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Liberman, M. Charles. Universidad de Buenos Aires; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; Argentina
Fil: Boulter, Jim. University of California at Los Angeles. School of Medicine; Estados Unidos
description Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.
publishDate 2007
dc.date.none.fl_str_mv 2007-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/80009
Vetter, Douglas E.; Katz, Eleonora; Maison, Stéphane F.; Taranda, Julian; Turcan, Sevin; et al.; The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 51; 12-2007; 20594-20599
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/80009
identifier_str_mv Vetter, Douglas E.; Katz, Eleonora; Maison, Stéphane F.; Taranda, Julian; Turcan, Sevin; et al.; The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 51; 12-2007; 20594-20599
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0708545105
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2154476/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083151659532288
score 13.22299

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